The Ophthalmology Department at Emory University leads a multidisciplinary collaboration with the Georgia Institute of Technology, University of Nebraska, and University of Pennsylvania. This collaboration was formed to improve drug delivery to the posterior segment of the eye. Drug delivery to this target is a significant challenge in the treatment of retinal disorders. Methods for drug treatment of the globe include systemic administration, eye drops, and injection into the orbit. Drug dilution, ocular infection, endophthalmitis, and surgical damage such as retinal detachment can occur with these techniques. Given these drawbacks, we hypothesize that transscleral approaches are better for posterior segment drug delivery. We propose to develop novel transscleral drug delivery approaches that use nanoparticles, microneedles, fibrin sealant, ontophoresis, and electoporation. We will a) examine the physiology of transscleral drug transport, b) establish analytical methods to determine the distribution of low molecular weight drugs as well as macromolecules to the various regions of the posterior segment, and c) demonstrate delivery and therapeutic effectiveness in experimental animal models. The drugs to be tested are known to affect retinal diseases in basic science experiments, pre-clinical studies, or clinical studies. This project entails collaborative research among investigators from various disciplines including ophthalmology, engineering, and pharmaceutical sciences. Milestones: Theoretical models will be completed during the first year; these will be post-experimentally reassessed annually. Drug delivery systems are established in vitro already, and during the first year will produce data sets for model refinement and establish starting parameters for in vivo studies in the first and second years. Toxicity studies will be completed during the second and third years. Pharmacokinetic and pharmacodynamic data will be collected during the third through fifth years. In the fourth and fifth years efficacy data are obtained. By accomplishing these pre-clinical tests, we will discover and develop new routes for efficacious delivery of drugs to the eye. These delivery techniques should be safer and more effective than the state of the art. ? Ultimately, these results will guide us in enhancing drug treatments in ophthalmic practice. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Resource-Related Research Projects (R24)
Project #
5R24EY017045-03
Application #
7473829
Study Section
Special Emphasis Panel (ZEY1-VSN (05))
Program Officer
Neuhold, Lisa
Project Start
2006-08-01
Project End
2011-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
3
Fiscal Year
2008
Total Cost
$1,347,980
Indirect Cost
Name
Emory University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Chiang, Bryce; Wang, Ke; Ethier, C Ross et al. (2017) Clearance Kinetics and Clearance Routes of Molecules From the Suprachoroidal Space After Microneedle Injection. Invest Ophthalmol Vis Sci 58:545-554
Chiang, Bryce; Venugopal, Nitin; Grossniklaus, Hans E et al. (2017) Thickness and Closure Kinetics of the Suprachoroidal Space Following Microneedle Injection of Liquid Formulations. Invest Ophthalmol Vis Sci 58:555-564
Chiang, Bryce; Venugopal, Nitin; Edelhauser, Henry F et al. (2016) Distribution of particles, small molecules and polymeric formulation excipients in the suprachoroidal space after microneedle injection. Exp Eye Res 153:101-109
Chiang, Bryce; Kim, Yoo Chun; Edelhauser, Henry F et al. (2016) Circumferential flow of particles in the suprachoroidal space is impeded by the posterior ciliary arteries. Exp Eye Res 145:424-431
Chiang, B; Kim, Y C; Doty, A C et al. (2016) Sustained reduction of intraocular pressure by supraciliary delivery of brimonidine-loaded poly(lactic acid) microspheres for the treatment of glaucoma. J Control Release 228:48-57
Kim, Yoo Chun; Oh, Kyung Hee; Edelhauser, Henry F et al. (2015) Formulation to target delivery to the ciliary body and choroid via the suprachoroidal space of the eye using microneedles. Eur J Pharm Biopharm 95:398-406
Allen, Rachael S; Olsen, Timothy W; Sayeed, Iqbal et al. (2015) Progesterone treatment in two rat models of ocular ischemia. Invest Ophthalmol Vis Sci 56:2880-91
Allen, Rachael S; Sayeed, Iqbal; Cale, Heather A et al. (2014) Severity of middle cerebral artery occlusion determines retinal deficits in rats. Exp Neurol 254:206-15
Kim, Yoo C; Grossniklaus, Hans E; Edelhauser, Henry F et al. (2014) Intrastromal delivery of bevacizumab using microneedles to treat corneal neovascularization. Invest Ophthalmol Vis Sci 55:7376-86
Kim, Yoo C; Edelhauser, Henry F; Prausnitz, Mark R (2014) Targeted delivery of antiglaucoma drugs to the supraciliary space using microneedles. Invest Ophthalmol Vis Sci 55:7387-97

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